For medical therapy of cerebral infarction (ischemic stroke), solving thrombus that caused cerebral infarction as early in the stage as possible after crisis is considered to be the most effective first selection. It is widely accepted that the sooner the restart of blood flow by dissolving the thrombus, the higher the effect of therapy becomes and the less the subsequent sequelae (dysphasia, paralysis, etc.) become.
As thrombolytic agents, urokinase (UK), streptokinase (SK), tissue plasminogen activator (TPA) having high thrombus affinity, etc. are used to dissolve thrombus. It is considered effective to apply such a thrombolytic agent within three hours after the crisis, and results of the therapy to patients show that improvement of symptoms by 30 to 40% has been observed by neurological evaluation at three months after the crisis.
Currently, improvement researches of the therapeutic technique by thrombolysis are being carried out principally in two directions below. The first improvement research of the therapeutic technique aims at improvement of a thrombolysis effect in a therapeutic time window that means a stage when a curative effect is expectable, namely, shortening of a thrombolysis time and restoration from penumbra (a state in which cerebral nerve cells are under ischemia). The second improvement research of the therapeutic technique aims at protecting cerebral nerve cells and further extending a time of the therapeutic time.
As a method for enhancing the thrombolysis effect by a thrombolytic agent, shortening a thrombolysis time, shortening a time from the crisis to recanalization of blood, and further reducing a dose of the thrombolytic agent from intravenous infusion by drip, there is proposed a method for promoting thrombolysis by irradiating the ultrasonic wave onto the embolic site (a portion in which thrombus occurred) and utilizing its ultrasonic energy.
As the thrombo-lysis method using the ultrasonic wave together, the following two methods have been proposed. The catheter ultrasonic irradiation method in which a catheter with an ultrasonic transducer on its point is inserted into blood vessel and the ultrasonic wave is irradiated onto a vicinity of the embolic site or across the embolic site, and the trans-cranial ultrasonic irradiation method in which the ultrasonic wave is irradiated toward the embolic site from the surface of the human body. The latter method includes a method that was applied by the present applicant and laid open as Japanese Laid Open Patent Publication No. 2004-024668.
It is found that the catheter ultrasonic irradiation method described above causes the following inconveniences in the case of applying it to actual therapy.
The first point is that in order to insert a catheter near the embolic site in a percutaneous transluminal manner, it is necessary to perform angiography by the X-ray contrastradiography or the digital subtraction angiography (DSA) and check an insertion status of the catheter. However, such a large-sized image display is not widely spread, there is a limit in applying these methods to patients.
The second point is that the ultrasonic transducer attached on the point of a catheter has low electroacoustic conversion efficiency and is easy to generate heat, and therefore has a high risk of promoting blood coagulation.
The third point is that, in the case where thrombus occurs in a peripheral vessel system, not in a main vessel system, the ultrasonic transducer provided on the point of the catheter cannot reach to targeted thrombus.
The fourth point is that, when targeted thrombus could be dissolved, if its fragment will flow into a peripheral vessel system and another thrombus will be generated in the peripheral vessel system, there will be no countermeasure.
The fifth point is that, since diagnostic and monitoring ultrasonic beams that have no therapeutic effects at all are simultaneously irradiated onto an ischemic area (infarction area) of a peripheral vessel system distal to the embolic site, side effects thereby are predictable.
On the other hand, the latter, the transcranial ultrasonic irradiation method does not produce the above-mentioned first to third points of inconveniences that are considered disadvantages of the catheter ultrasonic irradiation method described above, and so these disadvantages are solved.
However, it has become clear that the transcranial ultrasonic irradiation method produces following sixth and seventh points of inconveniences as will be described below.
The sixth point is that, although a low-frequency ultrasonic wave easily passes through the cranium, an ultrasonic beam irradiated into the cranium from the outside through one side thereof is reflected on the internal surface of the cranial bone on the other side, and the irradiated beam and the reflected beam interfere with each other to produce an acoustic resonant state inside the cranium, causing a temperature rise of the brain tissue.
The seventh point is that an ultrasonic beam irradiated into the inside of the cranium and a beam reflected on the internal surface of the cranial bone on the other side interfere with each other to produce a standing wave, and accordingly there is the possibility of generating an area where acoustic intensity increases abnormally at a spot inside the cranium, namely the so-called hot spot, which gives rise to risks of destruction of brain cells, occurrence of intracerebral hemorrhage, destruction of nerve tissue, etc.
Especially, the above-mentioned seventh point is a fatal side effect, that is, it is considered that occurrence of intracerebral hemorrhage results from a standing wave of the ultrasonic wave irradiated into the cranium.